Exendins and Exendin Agonists Modified with Polyamino Acids
First Claim
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1. A compound comprising exendin-4 linked to a polylysine through a C-terminal amino acid on the exendin-4;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51.
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Abstract
Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more molecular weight increasing compounds, for example, polyamino acids, polyethylene glycol polymers, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.
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Citations
20 Claims
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1. A compound comprising exendin-4 linked to a polylysine through a C-terminal amino acid on the exendin-4;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51.
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
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2. A pharmaceutical composition comprising (A) a compound which comprises exendin-4 linked to a polylysine through a C-terminal amino acid on the exendin-4;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51; and
(B) a pharmaceutically acceptable carrier. - View Dependent Claims (3, 4)
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
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5. A pharmaceutical composition comprising (A) a compound which comprises exendin-4 linked to a polylysine through (i) a C-terminal amino acid on the exendin-4, (ii) an internal lysine amino acid on the exendin-4, (iii) an internal aspartic acid amino acid on the exendin-4, (iv) an internal glutamic acid amino acid on the exendin-4, (v) an internal cysteine amino acid on the exendin-4, or (vi) an N-terminal amino acid on the exendin-4;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51; and
(B) a pharmaceutically acceptable carrier. - View Dependent Claims (6, 7, 8, 9, 10, 11)
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
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12. A pharmaceutical composition comprising (A) a compound which comprises exendin-4 linked to a polyamino acid through a C-terminal amino acid on the exendin-4;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51; and
(B) a pharmaceutically acceptable carrier. - View Dependent Claims (13, 14, 15, 16)
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
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17. A pharmaceutical composition comprising (A) a compound which comprises exendin-4 linked to a polyamino acid through (i) a C-terminal amino acid, (ii) an internal lysine amino acid, (iii) an internal aspartic acid amino acid, (iv) an internal glutamic acid amino acid, (v) an internal cysteine amino acid, or (vi) an N-terminal amino acid;
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
2 or 51; and
(B) a pharmaceutically acceptable carrier. - View Dependent Claims (18, 19, 20)
- wherein the exendin-4 comprises the amino acid sequence of SEQ ID NO;
Specification